DESCRIPTION (From the Applicant's Abstract): An extensive body of literature links stress and activation of the hypothalamic-pituitary-adrenal (HPA) axis with human affective disorders and disease, with special emphasis on the effect of early-life stressors (ELS) on the later development of psychological and psychiatric disorders. As the initiating neurohormone in the HPA axis, the role of corticotropin releasing factor (CRF) in mediating behavioral and hormonal alterations in animal models of these disorders has fallen under investigation. Building on the literature that links serotonin (5-HT) and CRF in human disease and corresponding animal models, the current set of experiments will test the hypothesis that CRF and 5-HT have a unique relationship in postnatal development (preweaning period) such that they work together to mediate the acute effects of neonatal isolation (a potent and naturalistic ELS). The first set of experiments will establish the ontogenic development of type 1 and type 2 CRF receptors (CRFRs) in the midbrain raphe of rat pup using receptor autoradiography. The second set will determine the degree of activation of the paraventicular nucleus of the hypothalamus (PVN) and the raphe nuclei in isolation stress using dual-label immunocytochemistry of cFos and CRF or 5-HT. Finally, we will demonstrate a unique, functional connection between the raphe and the PVN in mediating the acute effects of neonatal isolation stress by examining the effect of ablation of CRFR and 5-HT-containing cell bodies on raphe and PVN cFos activation, respectively.